Angiotensin II type 1 receptor blocker inhibits arterial calcification in a pre-clinical model
Angiotensin II type 1 receptor blocker inhibits arterial calcification in a pre-clinical model
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DOI：
10.1093/cvr/cvq391
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发表时间：
2011-04-01
影响因子：
10.8
通讯作者：
Rogers, Kem A.
中科院分区：
文献类型：
--
作者：
Armstrong, Zachary B.;Boughner, Derek R.;Rogers, Kem A.
动脉钙化是多种疾病的常见并发症，是死亡率的强预测因子。动脉钙化的机制尚未完全了解，因此，目前没有药物治疗可以阻止其进展。本研究的目的是探讨血管紧张素II（AngII）1型受体阻滞剂（ARB）对动脉calculation.Methods和结果的影响雄性新西兰白色兔喂致动脉粥样硬化饮食诱导动脉粥样硬化和动脉钙化超过12周的时间，与ARB在最后4周管理。使用临床相关的微型计算机断层扫描，我们发现与对照组相比，喂食致动脉粥样硬化饮食的动物显示出广泛的动脉钙化。相比之下，ARB给药完全抑制了钙化（胆固醇组和ARB组分别为2.80 +/- 1.17 vs. 0.01 +/- 0.01%钙化组织; n = 6和5; P < 0.05）。钙化区域的特征在于骨形态发生蛋白2、骨钙素和AngII 1型受体的上调以及伴随的α-平滑肌肌动蛋白的下调，与从血管细胞到成骨细胞的表型转换一致结论血管紧张素受体阻断剂通过阻断血管成骨抑制动脉钙化，ARB可能是一种新的治疗方法为患有血管钙化的患者提供选择。
Aims Arterial calcification is a common complication of several disorders and is a strong predictor of mortality. The mechanism underlying arterial calcification is not fully understood and as such, no pharmaceutical therapies are currently available which impede its progression. The aim of this study was to investigate the effects of an angiotensin II (AngII) type 1 receptor blocker (ARB) on arterial calcification.Methods and results Male New Zealand White rabbits were fed an atherogenic diet to induce atherosclerosis and arterial calcification over a period of 12 weeks, with an ARB administered in the final 4 weeks. Using clinically relevant micro-computed tomography, we found that animals fed the atherogenic diet displayed extensive arterial calcification when compared with control. In contrast, administration of the ARB completely inhibited calcification (2.80 +/- 1.17 vs. 0.01 +/- 0.01% calcified tissue in cholesterol and ARB-treated, respectively; n = 6 and 5; P < 0.05). Calcified regions were characterized by up-regulation of bone morphogenetic protein 2, osteocalcin, and the AngII type 1 receptor and concomitant down-regulation of a-smooth muscle actin, consistent with a phenotypic switch from vascular to osteoblast-like cells.Conclusion These data provide the first evidence that angiotensin receptor blockade can inhibit arterial calcification by disrupting vascular osteogenesis and suggest that ARBs may be a novel treatment option for patients suffering from vascular calcification.